Fig. 1: RTKs involvement in cell survival.
From: Therapeutic advances in the targeting of ROR1 in hematological cancers
Ligand-induced receptor dimerization allows the transphosphorilation of the intracellular tyrosine kinase domain, which leads to the activation of multiple pathways. GRB2 is recruited and subsequently binds and recruits SOS, which facilitates the exchange of GDP for GTP on RAS. RAS-GTP, the active form of RAS, initiates downstream signaling via /Raf/MEK/ERK pathway, promoting survival. RAS-GTP activates the PI3K/AKT pathway, leading to IKK tagging IκB for proteasomal degradation, which allows NF-κB to translocate to the nucleus and promote the expression of survival genes. On the other hand, AKT can inhibit FoxO, limiting apoptosis. Moreover, JNK and SRC are activated through receptor phosphorylation, promoting cell survival by enhancing the expression of survival genes like c-Jun and activating transcription factors such as STAT3. The activation of RTK also inhibits ASK1, preventing the activation of its downstream effector p38, which would otherwise promote apoptosis. (Created with BioRender.com).
